The research plan consists of two major projects. The first is to define the physiologic responses of the feline ileocecal sphincter (ICS) to feeding and to local stimuli such as distension, and to determine the contribution of various components of the anatomic ICS to these physiologic responses. These studies will contribute to an understanding of the integrative role, if any, of the ICS to the differing functions of the ileum and colon. The project consists of using three methods, an in vivo method and two in vitro methods to examine these problems. Discrepancy exists in the literature between studies performed in vivo and in vitro. The proposed studies will be directed to determine the reason for such discrepancies. The pathways mediating ICS relaxation to proximal distension, and contraction to distal distension will be defined. The effect of many peptides which are either released after meals or have been described to be present in the ICS, and their sites of action will be examined in vivo and in vitro. The integrative function of the ileum, ICS and colon in this area will be examined using myotomy techniques in vivo and in vitro. In addition, the possible role of vasoactive intestinal peptide as the neurotransmitter mediating relaxation at the ICS will be studied. The second major project of this research plan is the development of the technique of autoradiography of peptide receptors in the gastrointestinal tract. The methodology for autoradiography of opiate-, substance P-, bombesin-, as well as cholinergic and adrenergic receptors will be determined. This technique has not previously been applied to the gastrointestinal tract with respect to neuropeptides and neurotransmitters relevant to gastrointestinal motility. Quantitative autoradiography will allow the comparison of receptor sites and densities in different areas of the gastrointestinal tract and allow a comparison of the receptor population with physiologic responses in vivo and in vitro.